Plasma alpha 1-antitrypsin (alpha 1-AT) inhibits the activity of trypsin and related proteolytic enzymes. An interesting relationship between the plasma levels of alpha 1-AT and two pathological conditions has been observed in humans: unusually low levels of alpha 1-AT are found in the plasma of patients with an adult form of pulmonary emphysema and with a childhood form of cirrhosis of the liver. Moreover, increased amounts of alpha 1-AT have been noted in the livers of these patients, indicating the glycoprotein is being synthesized but not released from the parenchymal cells. One likely explanation of the problem of transport is the occurrence of an abnormality in the attachment and completion of the carbohydrate moiety to the polypeptide chain of alpha 1-AT. We have purified and begun characterization of this glycoprotein from normal human plasma. We propose to perform similar studies on the protein variant from pulmonary emphysema patients who have low levels and or inactive types of alpha 1-AT in their plasmas. These studies will include determination of molecular weight, electrophoretic mobility, isoelectric point, amino acid and carbohydrate compositions, subunit structure and its antiproteolytic enzyme activities. The nature of the bond linking the carbohydrate unit(s) to the peptide chain will be investigated. Ultimately, the amino acid and carbohydrate sequences will be examined. Characterization of the carbohydrate moiety of the variant will be of utmost importance since, as in other glycoproteins, it may be vitally important in transport processes. In this way we hope to gain an insight into the relationship between the structure and function of alpha 1-AT and thus better understand the pathologies of pulmonary emphysema and childhood cirrhosis of the liver on a molecular level.